30% or 60% Oxygen at Birth to Improve Neurodevelopmental Outcomes in Very Low Birthweight Infants

NCT03825835 | Recruiting DMC

• 1 other identifier: Pro00083931
• Study Type: interventional
• Target: 1,200
• Locations: 3 countries
• Sites: 21

Brief Summary

Preterm birth, or birth before 37 weeks' gestation, is increasingly common, occurring in 8 percent of pregnancies in Canada. Preterm birth is associated with many health complications, particularly when the birth happens before 29 weeks' gestation. At this gestational age, the lungs are not fully developed and it is not uncommon for infants to have problems breathing at the time of birth. One complication that can arise is when an infant stops breathing and needs to be resuscitated. When preterm babies need to be resuscitated doctors must take special care because of the small infant size and the immaturity of the brain and lungs. Oxygen is used to resuscitate babies who need it, but unfortunately there is disagreement about the best oxygen concentration to use. Oxygen concentration is important because both too much and too little oxygen can cause brain injury. This research aims to fill this knowledge gap by participating in an international clinical trial to compare the effects of resuscitating babies less than 29 weeks' gestational age with either a low oxygen concentration or a high oxygen concentration. The oxygen concentrations have been selected using the best available knowledge. This will be a cluster randomized trial where each participating hospital will be randomized to either 30 or 60 percent oxygen for the recruitment of 30 infants, and afterwards randomized to the other group for the recruitment of another 30 infants. After the trial, the investigator will determine whether the babies resuscitated with low oxygen or those resuscitated with high oxygen have better survival and long-term health outcomes. This research fills a critical knowledge gap in the care of extremely preterm babies and will impact their survival both here in Canada and internationally.

Conditions

Premature Infant; Respiratory Distress Syndrome in Premature Infant; Neurodevelopmental Outcome

Keywords

Delivery Room; Resuscitation; Premature Infant; Oxygen

Outcome Measures

Primary Outcomes (1)

• Number of participants with composite outcome of all-cause mortality or the presence of a major neurodevelopmental outcomes

  Defined as any one of the following: Mortality or (i) cerebral palsy with an inability to walk unassisted; (ii) major developmental delay involving cognition or language; or (iii) visual (cannot fixate/legally blind, or corrected acuity \< 6/60 in both eyes) or hearing impairment (requiring a hearing aid or cochlear implants).

  24+/- 6 months corrected age

Secondary Outcomes (19)

• Number of intubation in the delivery room

  first 15 minutes after birth

• Death in the Neonatal Intensive Care Unit

  During admission in the Neonatal Intensive Care Unit; no exact time frame can be given as this can happen after 1 day, 1 week, 1 months or up to 2-3 month. again deepening on gestational age and policy for transferring infants at participating centres.

• Number of participants who died in the delivery room

  During resuscitation in the delivery room; for lay people: this time frame might be 10min or 1-3 hours, depending on the approaching each participating hospital

• Number of participants with severe brain injury on cranial ultrasound

  During NICU admission (up to 6 months)

• Number of participants with severe retinopathy of prematurity stage 3 or higher

  During NICU admission (up to 6 months)

Study Arms (2)

30% group

ACTIVE COMPARATOR

Infants in the 30% oxygen group will remain in 30% oxygen (O2) until 5 min of age. At 5 min of age, the clinical team will assess oxygen saturation (SpO2). If SpO2 is \<85%, O2 should be increased by 10-20% every 60 sec to achieve SpO2 of 85% or greater or a SpO2 of 90-95% at 10 min of age. If SpO2 are greater than 95% at or before 5 min of age, O2 should be decreased stepwise (every 60 sec) with an aim to maintain SpO2 of 85% or greater during 5-10 min of age or 90-95% at and beyond 10 min of age. Intervention: Infants randomized to the 30% oxygen group will receive 30% oxygen at birth for the first 5 minutes. At 5 minutes oxygen can be adjusted as needed.

Drug: 30% oxygen group

60% group

EXPERIMENTAL

Infants in the 60% oxygen group will remain in 60% oxygen (O2) until 5 min of age. At 5 min of age, the clinical team will assess oxygen saturation (SpO2). If SpO2 is \<85%, O2 should be increased by 10-20% every 60 sec to achieve SpO2 of 85% or greater or a SpO2 of 90-95% at 10 min of age. If SpO2 are greater than 95% at or before 5 min of age, O2 should be decreased stepwise (every 60 sec) with an aim to maintain SpO2 of 85% or greater during 5-10 min of age or 90-95% at and beyond 10 min of age. Intervention: Infants randomized to the 60% oxygen group will receive 60% oxygen at birth for the first 5 minutes. At 5 minutes oxygen can be adjusted as needed.

Drug: 60% oxygen group

Interventions

30% oxygen group DRUG

Infants in the 30% oxygen group will remain in 30% oxygen (O2) until 5 min of age. At 5 min of age, the clinical team will assess oxygen saturation (SpO2). If SpO2 is \<85%, O2 should be increased by 10-20% every 60 sec to achieve SpO2 of 85% or greater or a SpO2 of 90-95% at 10 min of age. If SpO2 are greater than 95% at or before 5 min of age, O2 should be decreased stepwise (every 60 sec) with an aim to maintain SpO2 of 85% or greater during 5-10 min of age or 90-95% at and beyond 10 min of age. Intervention: Infants randomized to the 30% oxygen group will receive 30% oxygen at birth for the first 5 minutes. At 5 minutes oxygen can be adjusted as needed.

30% group

60% oxygen group DRUG

Infants in the 60% oxygen group will remain in 60% oxygen (O2) until 5 min of age. At 5 min of age, the clinical team will assess oxygen saturation (SpO2). If SpO2 is \<85%, O2 should be increased by 10-20% every 60 sec to achieve SpO2 of 85% or greater or a SpO2 of 90-95% at 10 min of age. If SpO2 are greater than 95% at or before 5 min of age, O2 should be decreased stepwise (every 60 sec) with an aim to maintain SpO2 of 85% or greater during 5-10 min of age or 90-95% at and beyond 10 min of age. Intervention: Infants randomized to the 60% oxygen group will receive 60% oxygen at birth for the first 5 minutes. At 5 minutes oxygen can be adjusted as needed.

60% group

Eligibility Criteria

• Age: 0 Minutes - 10 Minutes
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infants born at 23 0/7 weeks to 28 6/7 weeks' gestational age who will receive full resuscitation and are without major congenital abnormalities

You may not qualify if:

• Infants who are outborn - initial resuscitation not performed at the study centre
• Infants who are not born within the eligible gestational age range- this trial is specific to preterm infants
• Infants who are born with a major congenital abnormality- congenital abnormalities may affect oxygenation or neurodevelopmental outcomes
• Infants who will not receive full resuscitation at birth- these infants will not receive resuscitation

Sponsors & Collaborators

• University of Alberta: lead
• University of Toronto: collaborator
• University of Sydney: collaborator
• Dalhousie University: collaborator
• McMaster University: collaborator
• University of Manitoba: collaborator
• McGill University: collaborator
• University of Calgary: collaborator
• Memorial University of Newfoundland: collaborator
• University College Cork: collaborator
• University of British Columbia: collaborator
• Laval University: collaborator
• Université de Montréal: collaborator
• University of Ottawa: collaborator
• Queen's University: collaborator
• Université de Sherbrooke: collaborator

Study Sites (21)

Foothills Hospital

Calgary, Alberta, Canada

ACTIVE NOT RECRUITING

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

ACTIVE NOT RECRUITING

BC Children

Vancouver, British Colubia, Canada

RECRUITING

Health Sciences

Winnipeg, Manitoba, Canada

RECRUITING

Janeway Children's Health and Rehabilitation Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

ACTIVE NOT RECRUITING

Newborn Health - IWK Health Centre

Halifax, Nova Scotia, Canada

ACTIVE NOT RECRUITING

Neonatal Intensive Care Unit - Hamilton Health Sciences

Hamilton, Ontario, L8S 4K1, Canada

ACTIVE NOT RECRUITING

Queen's University

Kingston, Ontario, K7L 3N6, Canada

WITHDRAWN

CHEO

Ottawa, Ontario, Canada

ACTIVE NOT RECRUITING

Neonatal Intensive Care Unit - Mount Sinai Hospital

Toronto, Ontario, Canada

ACTIVE NOT RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

ACTIVE NOT RECRUITING

McGill Univeristy

Montreal, Quebec, Canada

ACTIVE NOT RECRUITING

Chu University Laval

Québec, Quebec, Canada

RECRUITING

Université de Sherbrooke

Sherbrooke, Quebec, J1N 3C6, Canada

RECRUITING

University College Cork

Cork, Ireland

RECRUITING

Hospital Germans Tries i Pujol

Barcelona, Spain

WITHDRAWN

Hospital Universitario Dexeus

Barcelona, Spain

WITHDRAWN

Hospital de la Arrixaca

El Palmar, Spain

WITHDRAWN

Hospital Las Palmas

Las Palmas de Gran Canaria, Spain

WITHDRAWN

Hospital de Asturias

Oviedo, Spain

WITHDRAWN

Hospital Universitario Materno Infantil Miguel Servet

Zaragoza, Spain

WITHDRAWN

Related Publications (1)

• Schmolzer GM, Asztalos EV, Beltempo M, Boix H, Dempsey E, El-Naggar W, Finer NN, Hudson JA, Mukerji A, Law BHY, Yaskina M, Shah PS, Sheta A, Soraisham A, Tarnow-Mordi W, Vento M; behalf of the HiLo trial collaborators. Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18-24 months in very low birthweight infants? Trials. 2024 Apr 4;25(1):237. doi: 10.1186/s13063-024-08080-2.

  PMID: 38576007 DERIVED

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Georg Schmolzer, MD, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Georg Schmolzer, MD, PhD

CONTACT

7807354647; schmolze@ualberta.ca

Barb Kamstra, RN

CONTACT

7807354647; Barb Kamstra <Barbara.Kamstra@albertahealthservices.ca>

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessed will be unaware of group allocation
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2019
• First Posted: January 31, 2019
• Study Start: June 27, 2022
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 30, 2029
• Last Updated: May 26, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: after the publication of the primary results indefinitely
• Access Criteria: Other researchers can email the PI for more information at georg.schmoelzer@me.com

Locations

ES (6); IE (1); CA (14)